Abstracts

RATIONALE: Levetiracetam(LEV) is an approved adjunctive treatment of partial onset seizures in adults. Neuropsychiatric adverse events, and non-clinically significant hematologic abnormalities were reported during clinical trials. Following FDA approval, the drug has also been used in broader groups of patients with epilepsy. We aimed first, to assess adverse events (AE[ssquote]s) of LEV in the general population. Secondly, to evaluate the impact in the population with known cognitive, psychiatry, and/or behavioral problems prior to LEV treatment.
METHODS: We reviewed the PADS (Postmarketing Antiepileptic/Device Drug Survey), a prospective database from 17 epilepsy centers to identify the population treated with LEV. Neuropsychiatric history was recorded at LEV initiation. AE[ssquote]s, serious AE[ssquote]s, discontinuation, and reason for discontinuation were determined at follow-up visits.
RESULTS: N=91. Follow-up period: 4-46 weeks, mean: 16 weeks. AE[ssquote]s were reported in 69/91 (76%) subjects: fatigue 20 (29%), behavior (anxiety, aggressive behavior, irritability) 8 (12%), dizziness 7/69 (10%), nausea/upper GI Symptoms 6, ataxia 4, psychomotor slowing 3, diplopia 2, insomnia 2, weight change 2 . Headache, blurred vision, rash, lower GI symptoms, tremor, numbness, constipation, tingling, alertness, joint pain, eye irritation, each 1 %.
There were 0 reports of nephrolithiasis, infection, weakness and sodium imbalance. Two serious AE[ssquote]s: suicide attempt and syncope.
LEV was discontinued in 24/91 (26%) for the following reasons: Loss of efficacy (LOE) 5, behavior 5, fatigue 4, increased seizures 2, nausea 2. Other reasons: dizziness , ataxia, sleepiness, insomnia and eye irritation.
Of 91 entries, 33 subjects with previous cognitive and/or behavioral problems were identified. Incidence of AE[ssquote]s 20/33 (61%) was lower in this group than in the general seizure population. Side effects: fatigue 7/20 (35%), dizziness, ataxia, increased behavioral problems, nausea, 2 each. The 2 serious AE[ssquote]s, suicide attempt and syncope, both occurred in this group. Diplopia, hematologic abnormalities, joint pain, and chills, 1 each.
LEV was discontinued in 7/33 (21%) subjects due to: behavior 2 (6%), LOE, fatigue, ataxia, nausea, and sleepiness, 1 each.
CONCLUSIONS: At this time, fatigue seems to be the commonest reported adverse symptom in patients treated with LEV, followed by dizziness and increased behavioral problems. Most of these symptoms were rated from mild to moderate, and improved over time. LEV is being used frequently in the population with underlying cognitive and/or behavioral problems. These subjects had a similar rate of behavioral side effects than the general epilepsy population. This data may change as the number of follow-up entries increases.
Support: UCB, Ortho-McNeil, Glaxo-wellcome, Elan Pharmaceuticals, Novartis.
Disclosure: Grant - UCB, Ortho-McNeil, Glaxo-wellcome, Elan Pharmaceuticals, Novartis. Consulting - UCB, Ortho-McNeil, Glaxo-wellcome, Elan Pharmaceuticals, Novartis. Honoraria - UCB, Ortho-McNeil, Glaxo-wellcome, Elan Pharmaceuticals, Novartis.